-
1.
Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach.
Dimitriadis, GD, Maratou, E, Kountouri, A, Board, M, Lambadiari, V
Nutrients. 2021;(1)
Abstract
Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.
-
2.
Blood glucose levels should be considered as a new vital sign indicative of prognosis during hospitalization.
Kesavadev, J, Misra, A, Saboo, B, Aravind, SR, Hussain, A, Czupryniak, L, Raz, I
Diabetes & metabolic syndrome. 2021;(1):221-227
-
-
Free full text
-
Abstract
BACKGROUND AND AIMS The measurement of vital signs is an important part of clinical work up. Presently, measurement of blood glucose is a factor for concern mostly when treating individuals with diabetes. Significance of blood glucose measurement in prognosis of non-diabetic and hospitalized patients is not clear. METHODS A systematic search of literature published in the Electronic databases, PubMed and Google Scholar was performed using following keywords; blood glucose, hospital admissions, critical illness, hospitalizations, cardiovascular disease (CVD), morbidity, and mortality. This literature search was largely restricted to non-diabetic individuals. RESULTS Blood glucose level, even when in high normal range, or in slightly high range, is an important determinant of morbidity and mortality, especially in hospitalized patients. Further, even slight elevation of blood glucose may increase mortality in patients with COVID-19. Finally, blood glucose variability and hypoglycemia in critically ill individuals without diabetes causes excess in-hospital complications and mortality. CONCLUSION In view of these data, we emphasize the significance of blood glucose measurement in all patients admitted to the hospital regardless of presence of diabetes. We propose that blood glucose be included as the "fifth vital sign" for any hospitalized patient.
-
3.
Effects of interrupting prolonged sitting on postprandial glycemia and insulin responses: A network meta-analysis.
Quan, M, Xun, P, Wu, H, Wang, J, Cheng, W, Cao, M, Zhou, T, Huang, T, Gao, Z, Chen, P
Journal of sport and health science. 2021;(4):419-429
Abstract
PURPOSE This study aimed to evaluate the effectiveness of physical activity (PA) interrupting prolonged sitting (PS) on postprandial glycemia and insulin responses among adults. METHODS PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, PsycINFO, and the China National Knowledge Infrastructure databases were searched through September 30, 2020. Randomized controlled trials (RCTs) that examined the effect of all forms of PA interrupting PS on postprandial glycemia and/or insulin responses among adults without chronic diseases were included in this study. The risk of bias of included studies was evaluated based on the Cochrane tool. A network meta-analysis was performed to estimate the summary standardized mean differences (SMDs) with 95% confidence intervals (95%CIs) with random effects. RESULTS Thirty crossover RCTs were included in our review. These RCTs included 9 types of interventions that interrupted PS. When compared to PS by itself, light-intensity PA intermittent interrupting (LPA-INT) PS and moderate-intensity PA intermittent interrupting (MPA-INT) PS significantly lowered postprandial glycemia (SMD = -0.46, 95%CI: -0.70 to -0.21; SMD = -0.69, 95%CI: -1.00 to -0.37, respectively) and significantly reduced postprandial insulin response (SMD = -0.46, 95%CI: -0.66 to -0.26; SMD = -0.47, 95%CI: -0.77 to -0.17, respectively). Results of the clustered ranking plot indicated that MPA-INT was the most effective intervention in lowering postprandial glycemia and insulin responses. CONCLUSION Replacing PS with MPA-INT or LPA-INT has a positive effect in reducing postprandial glycemia and insulin responses, with MPA-INT being the optimal intervention strategy.
-
4.
Glucose-lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase-4 inhibition.
Ahrén, B
Journal of diabetes investigation. 2021;(7):1128-1135
Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.
-
5.
Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives.
Rao, H, Jalali, JA, Johnston, TP, Koulen, P
Frontiers in endocrinology. 2021;:620045
Abstract
Diabetic retinopathy (DR) is a significant cause of vision loss and a research subject that is constantly being explored for new mechanisms of damage and potential therapeutic options. There are many mechanisms and pathways that provide numerous options for therapeutic interventions to halt disease progression. The purpose of the present literature review is to explore both basic science research and clinical research for proposed mechanisms of damage in diabetic retinopathy to understand the role of triglyceride and cholesterol dysmetabolism in DR progression. This review delineates mechanisms of damage secondary to triglyceride and cholesterol dysmetabolism vs. mechanisms secondary to diabetes to add clarity to the pathogenesis behind each proposed mechanism. We then analyze mechanisms utilized by both triglyceride and cholesterol dysmetabolism and diabetes to elucidate the synergistic, additive, and common mechanisms of damage in diabetic retinopathy. Gathering this research adds clarity to the role dyslipidemia has in DR and an evaluation of the current peer-reviewed basic science and clinical evidence provides a basis to discern new potential therapeutic targets.
-
6.
Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?
Papamargaritis, D, le Roux, CW
Nutrients. 2021;(3)
Abstract
Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy-the two most commonly performed bariatric procedures-and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9-39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.
-
7.
CGMS and Glycemic Variability, Relevance in Clinical Research to Evaluate Interventions in T2D, a Literature Review.
Breyton, AE, Lambert-Porcheron, S, Laville, M, Vinoy, S, Nazare, JA
Frontiers in endocrinology. 2021;:666008
Abstract
Glycemic variability (GV) appears today as an integral component of glucose homeostasis for the management of type 2 diabetes (T2D). This review aims at investigating the use and relevance of GV parameters in interventional and observational studies for glucose control management in T2D. It will first focus on the relationships between GV parameters measured by continuous glucose monitoring system (CGMS) and glycemic control and T2D-associated complications markers. The second part will be dedicated to the analysis of GV parameters from CGMS as outcomes in interventional studies (pharmacological, nutritional, physical activity) aimed at improving glycemic control in patients with T2D. From 243 articles first identified, 63 articles were included (27 for the first part and 38 for the second part). For both analyses, the majority of the identified studies were pharmacological. Lifestyle studies (including nutritional and physical activity-based studies, N-AP) were poorly represented. Concerning the relationships of GV parameters with those for glycemic control and T2D related-complications, the standard deviation (SD), the coefficient of variation (CV), the mean blood glucose (MBG), and the mean amplitude of the glycemic excursions (MAGEs) were the most studied, showing strong relationships, in particular with HbA1c. Regarding the use and relevance of GV as an outcome in interventional studies, in pharmacological ones, SD, MAGE, MBG, and time in range (TIR) were the GV parameters used as main criteria in most studies, showing significant improvement after intervention, in parallel or not with glycemic control parameters' (HbA1c, FBG, and PPBG) improvement. In N-AP studies, the same results were observed for SD, MAGE, and TIR. Despite the small number of N-AP studies addressing both GV and glycemic control parameters compared to pharmacological ones, N-AP studies have shown promising results on GV parameters and would require more in-depth work. Evaluating CGMS-GV parameters as outcomes in interventional studies may provide a more integrative dimension of glucose control than the standard postprandial follow-up. GV appears to be a key component of T2D dysglycemia, and some parameters such as MAGE, SD, or TIR could be used routinely in addition to classical markers of glycemic control such as HbA1c, fasting, or postprandial glycemia.
-
8.
Understanding Metabolic Memory: A Tale of Two Studies.
Miller, RG, Orchard, TJ
Diabetes. 2020;(3):291-299
-
-
Free full text
-
Abstract
The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.
-
9.
A State-of-the-Science Review of Arsenic's Effects on Glucose Homeostasis in Experimental Models.
Castriota, F, Rieswijk, L, Dahlberg, S, La Merrill, MA, Steinmaus, C, Smith, MT, Wang, JC
Environmental health perspectives. 2020;(1):16001
Abstract
BACKGROUND The prevalence of type 2 diabetes (T2D) has more than doubled since 1980. Poor nutrition, sedentary lifestyle, and obesity are among the primary risk factors. While an estimated 70% of cases are attributed to excess adiposity, there is an increased interest in understanding the contribution of environmental agents to diabetes causation and severity. Arsenic is one of these environmental chemicals, with multiple epidemiology studies supporting its association with T2D. Despite extensive research, the molecular mechanism by which arsenic exerts its diabetogenic effects remains unclear. OBJECTIVES We conducted a literature search focused on arsenite exposure in vivo and in vitro, using relevant end points to elucidate potential mechanisms of oral arsenic exposure and diabetes development. METHODS We explored experimental results for potential mechanisms and elucidated the distinct effects that occur at high vs. low exposure. We also performed network analyses relying on publicly available data, which supported our key findings. RESULTS While several mechanisms may be involved, our findings support that arsenite has effects on whole-body glucose homeostasis, insulin-stimulated glucose uptake, glucose-stimulated insulin secretion, hepatic glucose metabolism, and both adipose and pancreatic β-cell dysfunction. DISCUSSION This review applies state-of-the-science approaches to identify the current knowledge gaps in our understanding of arsenite on diabetes development. https://doi.org/10.1289/EHP4517.
-
10.
Glycemic Variability and CNS Inflammation: Reviewing the Connection.
Watt, C, Sanchez-Rangel, E, Hwang, JJ
Nutrients. 2020;(12)
Abstract
Glucose is the primary energy source for the brain, and exposure to both high and low levels of glucose has been associated with numerous adverse central nervous system (CNS) outcomes. While a large body of work has highlighted the impact of hyperglycemia on peripheral and central measures of oxidative stress, cognitive deficits, and vascular complications in Type 1 and Type 2 diabetes, there is growing evidence that glycemic variability significantly drives increased oxidative stress, leading to neuroinflammation and cognitive dysfunction. In this review, the latest data on the impact of glycemic variability on brain function and neuroinflammation will be presented. Because high levels of oxidative stress have been linked to dysfunction of the blood-brain barrier (BBB), special emphasis will be placed on studies investigating the impact of glycemic variability on endothelial and vascular inflammation. The latest clinical and preclinical/in vitro data will be reviewed, and clinical/therapeutic implications will be discussed.